Prognostic impact of activin subunit inhibin beta A in gastric and esophageal adenocarcinomas

Staudacher, J.J.; Arnold, A.; Kühl, A.A.; Pötzsch, M.; Daum, S.; Winterfeld, M.; Berg, E.; Hummel, M.; Rau, B.; Stein, U.; Treese, C.

Prognostic impact of activin subunit inhibin beta A in gastric and esophageal adenocarcinomas

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Item Type:	Article
Title:	Prognostic impact of activin subunit inhibin beta A in gastric and esophageal adenocarcinomas
Creators Name:	Staudacher, J.J., Arnold, A., Kühl, A.A., Pötzsch, M., Daum, S., Winterfeld, M., Berg, E., Hummel, M., Rau, B., Stein, U. and Treese, C.
Abstract:	PURPOSE: Adenocarcinomas of the esophagus (AEG) and stomach (AS) are among the most common cancers worldwide. Novel markers for risk stratification and guiding treatment are strongly needed. Activin is a multi-functional cytokine with context specific pro- and anti-tumorigenic effects. We aimed to investigate the prognostic role of activin tumor protein expression in AEG/ASs. METHODS: Tissue from a retrospective cohort of 277 patients with AEG/AS treated primarily by surgery at the Charité - Universitätsmedizin Berlin was collected and analyzed by immunohistochemistry using a specific antibody to the activin homodimer inhibin beta A. Additionally, we evaluated T-cell infiltration and PD1 expression as well as expression of PD-L1 by immunohistochemistry as possible confounding factors. Clinico-pathologic data were collected and correlated with activin protein expression. RESULTS: Out of 277 tumor samples, 72 (26.0%) exhibited high activin subunit inhibin beta A protein expression. Higher expression was correlated with lower Union for International Cancer Control (UICC) stage and longer overall survival. Interestingly, activin subunit expression correlated with CD4(+) T-cell infiltration, and the correlation with higher overall survival was exclusively seen in tumors with high CD4(+) T-cell infiltration, pointing towards a role of activin in the tumor immune response in AEG/ASs. CONCLUSION: In our cohort of AEG/AS, higher activin subunit levels were correlated with longer overall survival, an effect exclusively seen in tumors with high CD4(+) cell infiltration. Further mechanistic research is warranted discerning the exact effect of this context specific cytokine.
Keywords:	Gastric Adenocarcinoma, Esophageal Adenocarcinoma, Activin, INHBA, TGF-β Superfamily, Animals
Source:	BMC Cancer
ISSN:	1471-2407
Publisher:	BioMed Central
Volume:	22
Number:	1
Page Range:	953
Date:	5 September 2022
Official Publication:	https://doi.org/10.1186/s12885-022-10016-5
PubMed:	View item in PubMed

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